Process of producing larger cyanoalkanes from smaller ones



Patented Oct. 3, 1950 PROCESS OF PRODUCING LARGER CYANO- ALKANES FROMSMALLER ONES Morris S. Kharasch, Chicago, Ill., assignor to Eli Lillyand Company, Indianapolis, Ind., a corporation of Indiana No Drawing.Application July 11, 1949, Serial No. 104,144

11 Claims. 1

This invention relates to a process for producing larger cyanoalkaneswhich have a plurality of cyano (-CN) groups from smaller cyanoa-lkaneswhich have fewer cyano groups; and especially for producingdicyanoalkanes (succinonitriles) from monocyanoalkanes. Thecyanoalkanes, both those with the higher and those with the lowernumbers of cyano groups, include phenyl-substituted cyanoalkanes(phenyl) alkyl cyanides), in which there are one or more phenylsubstituents on the alkane.

In the initial smaller cyanoalkanes the alkane part must have ahydrogen-carrying aprimary carbon atom (defined below) linked directlytoa cyano group, and carrying either one or two hydrogen atoms; and in myprocess a hydrogen atom is removed from such an aprimary carbon atom,and the radicals resulting from such hydrogen removal are linkedtogether.

The present application is a continuation-inpart of my co-pendingapplication Serial N o. 581,- 946, filed March 9, 1945, and now patentNo. 2,- 477,671, granted August 2, 1949; which in turn was filed as acontinuation-in-part of my application Serial No. 503,172, filedSeptember 20, 1943, and now Patent No. 2,426,224, granted August 26,1947.

In carrying out my present invention, I treat the smaller cyanoalkanesat elevated temperature and in the substantial absence of water with adiacyl peroxide in which at least one of the acyl groups is an alkacylgroup of not more than four carbon atoms; preferably with diacetylperoxide. The diacyl peroxide is desirably a dialkacyl peroxide-that is,(as defined below), one containing two alkacyl groups, such as acetyl,propionyl, or butyryl. But the diacyl peroxide may be an aralkacylperoxide (defined below), for it is necessary only that there be onealkacyl group, so that the second acyl group may if desired be an aracylgroup, such for instance as benzoyl. The diacyl peroxide used can not bea diaracyl peroxide.

As used in this specification and its appended claims:

a. By alkacyl group I mean the acyl group of an alkyl carboxylic acid;

b. By aracyl group I mean the acyl group of an aromatic carboxylic acid;

0. By dialkacyl peroxide I mean a peroxide which both acyl groupsattached to the bivalent O-O- group are alkacyl groups;

(Z. By diaracyl peroxide I mean a peroxide in which both acyl groupsattached to the bivalent -OO group are aracyl groups;

e. By ar-alkacyl peroxide I mean a peroxide in which one acyl groupattached to the bivalent O-O- group is an alkacyl group and the other isan aracyl group.

1. By aprimary carbon atom I mean a carbon atom of the class consistingof secondary and terrtiary carbon atoms.

g. By primary or secondary or tertiary hydrogen atoms I mean hydrogenatoms directly attached to primary or secondary or tertiary carbon atomsrespectively;

It. By aprimary hydrogen atom I mean a hydrogen atom of the classconsisting of secondary and tertiary hydrogen atoms; and

2'. By cyanoalkane I mean an alkane having at least one cyano groupattached directly to a carbon atom of the alkane; whether or not thealkane also has a phenyl group attached to it either at the same carbonatom or a different carbon atom.

The preferred diacyl peroxide, as already noted, is diacetyl peroxide;which is effective in all cases and gives the highest yields. I can usedipropionyl peroxide and dibutyryl peroxide fairly effectively, theformer more effectively than the latter; and I can use diisobutyrylperoxide, but much less effectively and with rather poor results in somecases.

The diacyl peroxide does not itself combine with the initial smallercyanoalkanes. Instead, it acts exclusively to remove aprimary hydrogenatoms from them; whereupon the radicals remaining after that removal ofaprimary hydrogen atoms from the smaller cyanoalkanes unite one withanother by single carbon-to-carbon bonds, to produce larger cyanoalkanes(polycyanoalkanes) which save for the absence of the removed aprimaryhydrogen atoms are polymers constituting the sum of two or more originalsmaller arylalkanes.

The initial smaller cyanoalkanes to whichmy invention is applicable arethe lower cyanoalkanes (with one or more cyano substituents) having notto exceed 12 carbon atoms, and in which a cyano group is directlyattached to an aprimary alkane carbon atom carrying one or two hydrogenatoms, whether or not the alkane has also a phenyl substituent. Thealkane may be methane provided its single carbon atom has directlyattached to it not only the cyano group but also a phenyl group, as inbenzyl cyanide; but usually the alkane will have at least two alkanecarbon atoms, in order to make one which carries the cyano groupanaprimary carbon atom. This aprimary carbon atom must carry at least onehydrogen atom, which is all it can carry if the aprimary carbon atom isa tertiary carbon atom; but it that aprimary carbon is a secondarycarbon atom it may carry two hydrogen atoms.

In the reaction produced according to my process, in which a smallercyanoalirane is treated with a diacyl peroxide having at least one or"its acyl groups an alkacyl group, the diacyl peroxide (most desirablydiacetyl perox de) does not combine with the smaller cyanoalliane, ashas already been stated. But neither does it act as a mere catalyst, forthe reaction that involves the smaller cyanoalkane depends completelyfor its extent upon the amount of diacyl peroxide used. Further, theaction of the diacyl peroxide used is entirely different from the actionof either hydrogen peroxide or dibenzoyl peroxide.

What happens in the reaction or" the diacyl peroxide (using diacetylperoxide an example) and a smaller cyanoalkane is represented by themethyl radical of an aprimary hydrogen atom from the initial smallercyanoalkane, to produce methane and the free radical of that initialsmaller cyanoalkane. Equation 3 represents the combining (dimerizing) oftwo of the free radi cals of the initial smaller cyanoalkane, to form anew carbon-to-carbon bond, thus producing a larger cyanoalkane havingdouble the number of carbon atoms and double the number of cyano groupsof the initial smaller cyanoalkane.

By limiting the amount of diacetyl peroxide added, the largercyanoalkane of double the number of carbon atoms and double the numberof cyano groups may be obtained in high yields, often of the order of90% to 100% of the amount calculated on the basis of the diacetyl perox-I ide used.

The larger cyanoalkane with double the number of carbon atoms and doublethe number of cyano groups may in turn be treated with a suitable diacylperoxide (desirably diacetyl peroxide) to produce a second doubling,provided that after the first doubling there still remains in s thealkane a hydrogen-carrying aprimary carbon atom directly attached to acyano group; that aprimary carbon atom may be the same one as in theinitial reaction it in the initial cyanoalkane it was a secondary carbonatom carrying two hydrogen atoms, but not if it was a tertiary carbonatom, which can carry only a single hydrogen atom. Further, again withthe same proviso, by using a larger quantity of the diacyl peroxide inthe initial reaction with the original cyanoalkane, it is possible toget mixtures in which in addition to cyanoalkanes of double the numberof carbon atoms and cyano groups there are compounds of higher multiplesof the original number of carbon atoms and cyano groups, such as treblethe number, quadruple the number, quintuple the number, etc. With someinitial cyanoalkanes it is possible to limit substantially themultiplying of the number of carbon atoms and cyano groups to threefold(the trimer) but generally the multiplying of the number of carbon atomsand cyano groups is to double the number (the dimer) or to quadruple thenumber of carbon atoms and cyano groups (the tetramer, or the dimer ofthe dimer).

In some cases, when the cyanoalkane treated with a diacyl peroxidecontains more than one aprimary hydrogen atom, a mixture of two or moredimeric substances will result.

In carrying out the general reaction with the diacyl peroxide (desirablydiacetyl peroxide) it is usually desirable first to dissolve the diacylperoxide, in the cold (desirably about 10 0.), in a small portion of theinitial smaller cyanoalkane to be treated if that initial cyanoalkane isliquid, and then to add that solution very slowly, desirably drop bydrop, in the substantial absence of Water, to a larger quantity of theinitial cyanoalkane. If only the dimer is desired, there is generally aseveral-fold molecular excess of the initial cyanoalkane to be treatedover the diacyl peroxide.

Alternatively, the diacyl peroxide may be dissolved in the cold in asuitable solvent, such as carbon tetrachloride, and that cold solutionmay be added slowly to a heated and concentrated solution in the samesolvent of the initial smaller cyanoalkane to be treated. But thereaction in a third substance as a solvent is usually less desirablethan when the only compounds present are the diacyl peroxide and thecyanoalkane to be treated.

The followin are typical examples of the process of this invention,resulting in some instances in products which are themselves new.

Example 1.--P'reporation of afi-dimcthylsuccinom'trile In this examplepropionitrile is the initial cyanoalkane. In it the alkane carbon atomto which the cyano group is attached is a secondary carbon atom, andcarries tWo aprimary hydrogen atoms, whichare thus secondary hydrogenatoms.

Diacetyl peroxide, dissolved in propionitrile or in carbontetrachloride, is added slowly to proprionitrile (3-5 molecularequivalents on the basis of the diacetyl peroxide used) maintained at-95 C. The addition. of the peroxide requires about 2-3 hours, and theheating is continued until the reaction mixture no longer gives a testfor peroxide. The excess of propionitrile or carbon tetrachloride isremoved by distillation at reduced pressure. The material remaining isin large measure the desired a,5-dimethy1 succinonitrile, which may alsobe called 2,3-dicyanobutane.

The-reactions which occur are as follows? Example 2.-Preparation ofa,,8-diphen1/Zsuccc'nomtrile Example 1 is repeated, save that benzyl cyanide, CsH5CH2-CN, is used instead of propionitrile. A similar set ofreactions occurs, as follows:

The dimer, which is u,,8-diphenylsuccinonitrile, or1,2-diphenyl-1,2-dicyanoethane, also has two forms (raceniic and meso);which can readily be separated by making use of their different solubilities in alcohol.

Here again the product obtained may be limited substantially to thedimer, a,,8-diphenylsuccinonitrile, by keeping low the amount ofdiacetyl peroxide used; but higher polymers may be ob tained by usinglarger quantities of the diacetyl peroxide.

Example 3.-Prepamtion of a,p-dzfdecylsztccinonitrite Nitriles oflong-chain aliphatic radicals, such as dodecyl nitrile CH3 CH2 10CN, canalso be dimerized with the aid of diacetyl peroxide. By repeatingExample 1 on dodecyl nitrile, for example, the dimer isobtained-a,p-didecylsuccinonitrile. It has the following structure:

Here again two forms (racemic and meso) of the dimer,up-didecylsuccinonitrile, are produced in about equal quantities. Alongwith these two forms of the dimer, a higher-boiling material is Example4 Example 1 may be repeated with initial cyanoalkanes in which thecyano. group is attached to an intermediate carbon atom of an allzylchain, whether elsewhere branched or not, instead. of to an end carbonatomas in Examples 1 and 3; such for instance as Z-cyanopropane,Z-cyanobutane, 3cyanohexane, v3-cyano-4-methyl octane, 2-cyano-3-propylheptane, etc., so that the alkane carbon atom to which the cyano groupis directly attached is a. tertiary carbon atom. The dimers of these,(for only dimers are obtained), as: obtained. by my treatment with adiacyl peroxide at elevated. temperature and in the substantial ab senceof water, are analogs of that. given in Example 1; save that in thosedimers the carbon atoms Which carry the cyano groups are quaternarycarbon atoms instead of tertiary carbon atoms and so carry no hydrogenatoms-because of which fact there are no higher polymers than thedimers. For instance, by repeating Example 1 with 2-cyanopropane, as theinitial cyanoal- Kane, the reactions which occur are as follows: 11)

(13) CH3 CE:

I dimerizes l CHa-C-ON CHzG--ON OHa- CN This final product is obtainedin substantially quantitative yield; and is 2,3-dicyano-2,3-dimethylbutane. It is a White solid.

Erample 5.-Preparation of 2.,3-dicyano-2,3,-dz'- phenylbutane Example 2is repeated, save that 1-pheny1-1 cyanoethane OH; (CaH51HCNl is theinitial cyanoalkane instead of benzyl cyanide. Here also the carbon atomcarrying the cyano group is a tertiary carbon atom, so that the dimer isthe only polymer obtained. The reactions are similar to those of Example2, as follows:

This dimer, which is 2,3-dicyano-2',3-diphenylbutane, also has two forms(racemic and meso) which can readily be separated by making use of theirdifferent solubilities in alcohol. Here again, as in Example 4, theproduct obtained is limitedto thedimer, because upon thedimerizationthere; remains no aprimary hydrogen atom,

Example 6 Example 2 may be repeated on other phenylsubstitutedcyanoalkanes, both those with a phenyl group and a cyano group attachedto the same alkane carbon atom, as in Examples 2 and 5, and those with aphenyl group and a cyano group attached to different alkane carbonatoms. For instance, instead of the propionitrile of Example 2, or thel-phenyl-l-cyanoethane of Example 5, I may use l-cyano-2-phenyl ethane,or 2cyano-3phenyl pentane, or 2-cyano5 phenyl octane, etc. Ifl-cyano-2-phenyl ethane is used as the initial cyanoalkane, forinstance, and is treated with diacetyl peroxide in the manner ofprevious examples, reactions occur as follows:

This product of these reactions is the dimer,1,4-diphenyl-2,3-dicyanobutane.

The phenyl group attached to one of the aprimary carbon atoms of theinitial l-cyano-Z- phenylethane also produces some activation, withsomewhat different dimerization; to yield a 1,4-dicyano-2,3-diphenylbutane having the following structure:

Small amounts of some trimers and tetramers are also formed in thisreaction.

Emample 7 As already indicated, other dialkacyl peroxides than diacetylperoxide may be used in Examples 1 to 6. However, while dipropionyl,dibutyryl, and diisobutyryl peroxides will produce the products obtainedin those examples, the best results are with diacetyl peroxide.

The dialkacyl peroxide which in all cases gives the best yield ofdimers, trimers, and tetramers is diacetyl peroxide; because the freemethyl radical which comes from it is the most active of the free alkylradicals. The activity of other free alkyl radicals, produced in thedecomposition of higher dialkacyl peroxides, and therefore the yields ofdesired dimers, trimers, and tetramers, decreases as one proceed to thefree ethyl radical (from dipropionyl peroxide), the free propyl radical(from di-n-butyryl peroxide), the free isopropyl radical (fromdiisobutyryl peroxide), and the free tertiarybutyl radical (fromditrimethylacetyl peroxide) Thus the free tertiary-butyl radical is theleast reactive of all of these, and the yields of the desired productswhen it is used are negligible. In general, the free methyl radical ismost reactive; free primary-alkyl radicals are more reactive than freesecondary-alkyl radicals; free secondary-alkyl radicals are morereactive than free tertiary-alkyl radicals; and free alkyl radicals withfewer car bon atoms are more reactive than those with more carbon atoms.

Example 8 Instead of diacetyl peroxide or other dialkacyl peroxide, anar-alkacyl peroxide (or aromaticaliphatic peroxide) may be used; suchfor instance as acetyl benzoyl peroxide. The initial reaction in thiscase, to produce the free methyl radical, is as follows:

In this Example 8, as in Examples 1-6 inclusive, the free methyl radicalis set free, and is the thing which removes an aprimary hydrogen atomfrom the intial smaller cyanoalkane to give methane and the new freeradical of that initial smaller cyanoalkane; which in turn dimerizes toproduce the desired compound with double the number of carbon atoms anddouble the number of cyano groups. Essentially, therefore, there is nodii ference whether diacetyl peroxide or acetyl benzoyl peroxide isused; since in both cases free methyl radicals are produced, and thosefree methyl radicals react with the initial smaller cyanoalkane.

On the same basis, other ar-alkacyl peroxides (aliphatic-aromaticperoxides) may be used; such for instance as propionyl benzoyl peroxide,butyryl benzoyl peroxide, acetyl naphthoyl peroxide, acetylp-methylbenzoyl peroxide, or other peroxide of the general formula:

in which R represents an alkacyl group and R represents an aracyl group.These may be used in all of Examples 1 to 6, with the limitations givenin those examples for the alkacyl group. Furthermore, the highest yieldsare obtained when R is the acetyl group.

Example 9 Similarly, unsymmetrical dialkacyl peroxides may be used inall the examples in place of the symmetrical peroxides named. Examplesof these are:

Acetyl propionyl peroxide Acetyl hutyryl peroxide Propionyl laurylperoxide atoms and which are members of the class consisting of alkylcyanides and phenyl alkyl cyanides and in which an alkane carbon atomdirectly attached to a cyano group is an aprimary carbon atom carryingat least one hydrogen atom; which consists in treating the said smallercyanoalkane at elevated temperature and in the substantial absence ofwater with a diacyl peroxide in which at least one of the acyl groups isan alkacyl group of not more than four carbon atoms.

2. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the diacyl peroxide is adialkacyl peroxide.

3. The process of producing larger cyanoal- I kanes from smallercyanoalkanes as set forth in claim 1, in which an acyl group of thediacyl peroxide is the actyl group.

4. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the diacyl peroxide isdiacetyl peroxide.

5. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the diacyl peroxide is anaralkacyl peroxide.

6. The process of producing larger cyanoal- 10 kanes from smallercyanoalkanes as set forth in claim 1, in which the diacyl peroxide isbenzoyl acetyl peroxide.

7. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the smaller cyanoalkaneis an alkyl cyanide.

8. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the smaller cyanoalkaneis propionitrile.

9. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the smaller cyanoalkaneis dodecylnitrile.

10. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the smaller cyanoalkaneis a phenylalkyl cyanide.

11. The process of producing larger cyanoalkanes from smallercyanoalkanes as set forth in claim 1, in which the smaller cyanoalkaneis benzyl cyanide.

MORRIS S. KHARASCH.

No references cited.

Certificate of Correction Patent No. 2,524,319 October 3, 1950 MORRIS S.KHARASCH It is hereby certified that error appears in the printedspecification of the above numbered patent requiring correction asfollows:

Column 1, line 9, strike out the closing parenthesis after henyl; line50, before which insert in; column 5, line 46, for The before dimer readThis; column 6, line 29, Formula 11, for CH read 0H column 7, lines 32and 33, Formula 19, for

read

column 9, line 18, for actyl read acetyl;

and that the said Letters Patent should be read as corrected above, samemay conform to the record of the case in the Patent ()fiice. Signed andsealed this 9th day of January, A. D. 1951.

so that the [SEAL] THOMAS F. MURPHY,

Assistant Commissioner of Patents.

1. THE PROCESS OF PRODUCING LARGER CYANOALKANES WHICH HAVE A PLURALITYOF CYANO GROUPS FROM A SMALLER CYANOALKANES WHICH HAVE FEWER CYANOGROUPS AND NOT TO EXCEED 12 ALKANE CARBON ATOMS AND WHICH ARE MEMBERS OFTHE CLASS CONSISTING OF ALKYL CYANIDES AND PHENYL ALKYL CYANIDES AND INWHICH AN ALKANE CARBON ATOM DIRECTLY ATTACHED TO A CYANO GROUP IS ANAPRIMARY CARBON ATOM CARRYING AT LEAST ONE HYDROGEN ATOM; WHICH CONSISTSIN TREATING THE SAID SMALLER CYANOALKANE AT ELEVATED TEMPERATURE AND INTHE SUBSTANTIAL ABSENCE OF WATER WITH A DIACYL PEROXIDE IN WHICH ATLEAST ONE OF THE ACYL GROUPS IS AN ALKACYL GROUP OF NOT MORE THAN FOURCARBON ATOMS.